Perspectives on improving blood pressure control to reduce the clinical and economic burden of hypertension.

The clinical and economic burden of hypertension is high and continues to increase globally. Uncontrolled hypertension has severe but avoidable long-term consequences, including cardiovascular diseases, which are among the most burdensome and most preventable conditions in Europe. Yet, despite clear guidelines on screening, diagnosis and management of hypertension, a large proportion of patients remain undiagnosed or undertreated. Low adherence and persistence are common, exacerbating the issue of poor blood pressure (BP) control. Although current guidelines provide clear direction, implementation is hampered by barriers at the patient-, physician- and healthcare system levels. Underestimation of the impact of uncontrolled hypertension and limited health literacy lead to low adherence and persistence among patients, treatment inertia among physicians and a lack of decisive healthcare system action. Many options to improve BP control are available or under investigation. Patients would benefit from targeted health education, improved BP measurement, individualized treatment or simplified treatment regimens through single-pill combinations. For physicians, increasing awareness of the burden of hypertension, as well as offering training on monitoring and optimal management and provision of the necessary time to collaboratively engage with patients would be useful. Healthcare systems should establish nationwide strategies for hypertension screening and management. Furthermore, there is an unmet need to implement more comprehensive BP measurements to optimize management. In conclusion, an integrative, patient-focused, multimodal multidisciplinary approach to the management of hypertension by clinicians, payers and policymakers, involving patients, is required to achieve long-term improvements in population health and cost-efficiency for healthcare systems.

[Older care receivers with chronic pain : Cross-sectional study of gender-specific pain intensity and home-care provision in the city environment]. / Ältere Pflegebedürftige mit chronischen Schmerzen : Querschnittsstudie zur geschlechtsspezifischen Schmerzintensität und Versorgung in der großstädtischen Häuslichkeit.

BACKGROUND: Pain prevalence rates of up to 53% are found among older home-care recipients (aged ≥ 60 years). Of people affected by pain in Germany, care recipients comprise a relevant group with prevalence rates of around 70%. The available information on gender-specific pain experience shows a range of differing findings. OBJECTIVE: Our objective was to determine pain parameters of older care receivers in the big city environment who are capable of self-reporting, taking into account gender differences and relevant aspects of medical care and medication. MATERIAL AND METHODS: A cross-sectional study (structured interviews) was carried out among older (≥65 years) home-care recipients (German Social Security Code SGB XI) in Berlin, with chronic pain (n = 225), capable of self-reporting (MMST ≥ 18). Pain parameters were determined using the German version of the brief pain inventory (BPI-NHR). Multiple regression analysis was applied to test and explain how the severest pain was influenced by sociodemographic and medical parameters, mental and physical restrictions, and analgesic provision. RESULTS: Analyses showed an average pain intensity of 5.3 (SD ± 2.0). The severest pain averaged 7.0 (SD ± 2.2). Few indications of significant gender-based differences were found (e.g. pain location, number of medications). The final model identified the number of pain locations (≥14), everyday abilities, and pain medication (as needed, none) as being associated with the severest pain. Treatment achieved pain relief of over 70% in only 24.6% of cases among pain-affected care receivers. CONCLUSION: The findings indicate a significant level of pain experienced by older home-care recipients. Interdisciplinary care concepts are urgently needed.

[Pharmacology of non-opioid analgesics]. / Pharmakologie der Nichtopioidanalgetika.

Due to high prescription rates as well as the frequent use as over the counter drugs, it is of interest to consider non-opioid analgesics when evaluating the quality and appropriateness of a given overall medication. This article sums up the basic pharmacology and main adverse effects of these analgesics. Non-opioids can be further classified according to their additional mechanisms of action besides analgesia. High-dose acetylsalicylic acid, traditional nonsteroidal anti-inflammatory drugs, and coxibs exhibit antipyretic and anti-inflammatory properties. Acetaminophen and metamizole (dipyrone) are analgesics and antipyretic agents, while metamizole exhibits also spasmolytic effects. Capsaicin and intrathecal ziconotide are pure analgesics.

[Comments on the guidelines (2018) of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension]. / Kommentar zu den Leitlinien (2018) der Europäischen Gesellschaft für Kardiologie (ESC) und der Europäischen Gesellschaft für Hypertonie (ESH) für das Management der arteriellen Hypertonie.

Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League. In these comments national characteristics are worked out and the essential new aspects of the guidelines are critically discussed. These include, for example, the definition of hypertension, the importance of out of office blood pressure measurements, revised blood pressure targets, the modified algorithm for drug treatment and the relevance of device-based hypertension treatments. Important aspects for the management of hypertensive emergencies are also presented.

Effect of UMOD genotype on long-term graft survival after kidney transplantation in patients treated with cyclosporine-based therapy.

The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with renal function, chronic kidney disease and hypertension with the minor T-allele showing a protective effect. Hypertension and nephrotoxicity are adverse effects of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor kidneys associates with long-term graft survival in 393 Caucasian patients with stable graft function for more than 10 weeks after kidney transplantation treated with a cyclosporine-based maintenance therapy (mean graft survival 9 years). Presence of the donor T-allele had no effect on blood pressure, serum creatinine 1 year after transplantation, and on number of acute graft rejections during the first year. No significant effect on overall graft survival was observed in Kaplan-Meier analysis (P=0.65). In death-censored adjusted multivariate analysis, presence of donor T-allele associated with a significant lower hazard ratio of 0.67 (95% confidence interval: 0.46-0.97, P=0.05) for graft loss. This protective effect of the donor T-allele on graft loss observed in multivariate adjusted analysis justifies further investigations including patients treated with similar or other immunosuppressive regimens.

European guidelines on lifestyle changes for management of hypertension : Awareness and implementation of recommendations among German and European physicians.

BACKGROUND: In the 2013 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) guidelines for the management of arterial hypertension, six lifestyle changes for treatment are recommended for the first time with class I, level of evidence A. We initiated a survey among physicians to explore their awareness and consideration of lifestyle changes in hypertension management. METHODS: The survey included questions regarding demographics as well as awareness and implementation of the recommended lifestyle changes. It was conducted at two German and two European scientific meetings in 2015. RESULTS: In all, 1064 (37.4% female) physicians participated (806 at the European and 258 at the German meetings). Of the six recommended lifestyle changes, self-reported awareness was highest for regular exercise (85.8%) followed by reduction of weight (66.2%). The least frequently self-reported lifestyle changes were the advice to quit smoking (47.3%) and moderation of alcohol consumption (36.3%). Similar frequencies were observed for the lifestyle changes implemented by physicians in their care of patients. CONCLUSION: A close correlation between awareness of guideline recommendations and their implementation into clinical management was observed. European physicians place a stronger emphasis on regular exercise and weight reduction than on the other recommended lifestyle changes. Moderation of alcohol consumption is the least emphasized lifestyle change.

The importance of protein binding for the in vitro-in vivo extrapolation (IVIVE)-example of ibuprofen, a highly protein-bound substance.

A physiologically based human kinetic model (PBHKM) was used to predict the in vivo ibuprofen dose leading to the same concentration-time profile as measured in cultured human hepatic cells (Truisi et al. in Toxicol Lett 233(2):172-186, 2015). We parameterized the PBHKM with data from an in vivo study. Tissue partition coefficients were calculated by an algorithm and also derived from the experimental in vitro data for the liver. The predicted concentration-time profile in plasma was in excellent agreement with human experimental data when the liver partition coefficient was calculated by the algorithm (3.01) demonstrating values in line with findings obtained from human postmortem tissues. The results were less adequate when the liver partition coefficient was based on the experimental in vitro data (11.1). The in vivo doses necessary to reach the in vitro concentrations in the liver cells were 3610 mg using the best fitting model with a liver partition coefficient of 3.01 compared to 2840 mg with the in vitro liver partition coefficient of 11.1. We found that this difference is possibly attributable to the difference between protein binding in vivo (99.9 %) and in vitro (nearly zero) as the partition coefficient is highly dependent on protein binding. Hence, the fraction freely diffusible in the liver tissue is several times higher in vitro than in vivo. In consequence, when extrapolating from in vitro to in vivo liver toxicity, it is important to consider non-intended in vitro/in vivo differences in the tissue concentration which may occur due to a low protein content of the medium.

Tocilizumab-induced pancreatitis: case report and review of data from the FDA Adverse Event Reporting System.

WHAT IS KNOWN AND OBJECTIVE: Tocilizumab (TCZ) is a humanized monoclonal antibody acting against the IL-6 receptor. It is a drug used in the treatment of rheumatoid arthritis and can be either given intravenously every 4 weeks or subcutaneously once a week. Known adverse events (AE) associated with TCZ include: infections of the upper respiratory tract, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. Here, we present the first well-documented case of TCZ-induced acute pancreatitis (AP) and a systematic review of the literature including data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Patient data collection was performed within the Berlin Case-Control Surveillance Study. A literature search for TCZ-induced AP was conducted. Analysis of the FAERS database concerning TCZ-associated pancreatic AE from the period of 2009 until the first quarter of 2013 was conducted. RESULTS AND DISCUSSION: A 40-year-old man presented with a 2-day history of progressive upper abdominal pain with elevated serum lipase and triglyceride levels. Biliary pancreatitis was ruled out by abdominal sonography and CT scan. Cessation of intravenously administered TCZ resulted in improvement of the patient's condition and a decline in elevated laboratory values, suggesting a probable relationship between TCZ intake and AP. Analysis of the FAERS database retrieved 52 cases of TCZ-associated AP that accounted for 70% of all pancreatic AE in association with TCZ use. Further literature search detected three additional cases in which TCZ use was associated with AP. WHAT IS NEW AND CONCLUSION: Physicians should be aware of the probable association between TCZ use and AP. Targeted post-authorization studies are needed to confirm and quantify the risk of TCZ-induced AP.

[Pharmacovigilance in Germany : It is about time]. / Pharmakovigilanz in Deutschland : Es wird langsam Zeit.

BACKGROUND: Pharmacovigilance is defined as the activities relating to the detection, assessment, and prevention of adverse drug reactions (ADRs). Although its beginnings in Germany date back more than 50 years, a stagnation in this field has been observed lately. OBJECTIVES: Different tools of pharmacovigilance will be illustrated and the reasons for its stagnation in Germany will be elucidated. CURRENT DATA: Spontaneous reporting systems are an important tool in pharmacovigilance and are based on reports of ADRs from treating physicians, other healthcare professionals, or patients. Due to several weaknesses of spontaneous reporting systems such as underreporting, media bias, confounding by comorbidity or comedication, and due to the limited quality of the reports, the development of electronic healthcare databases was publicly funded in recent years so that they can be used for pharmacovigilance research. In the US different electronic healthcare databases were merged in a project sponsored by public means resulting in more than 193 million individuals. In Germany the establishment of large longitudinal databases was never conceived as a public duty and has not been implemented so far. Further attempts to use administrative healthcare data for pharmacovigilance purposes are severely restricted by the Code of Social Law (Section 75, Book 10). This situation has led to a stagnation in pharmacovigilance research in Germany. CONCLUSIONS: Without publicly funded large longitudinal healthcare databases and an amendment of Section 75, Book 10, of the Code of Social Law, the use of healthcare data in pharmacovigilance research in Germany will remain a rarity. This could have negative effects on the medical care of the general population.

Target organ damage and control of cardiovascular risk factors in hypertensive patients. Evidence from the multicenter ESTher registry.

AIMS: This study investigated the incidence of hypertensive target organ damage (TOD), control of cardiovascular risk factors, and the short-term prognosis in hypertensive patients under contemporary guideline-oriented therapy. PATIENTS AND METHODS: A total of 1,377 consecutive patients (mean age 58.2 ± 9.9 years, 82.2 % male) with arterial hypertension were included in the ESTher (Endorganschäden, Therapie und Verlauf - target organ damage, therapy, and course) registry at 15 rehabilitation clinics within the framework of the National Genome Research Network. Cardiovascular risk factors, medication, comorbidities, and glomerular filtration rate (GFR) were assessed. Left ventricular hypertrophy (LVH), left ventricular mass (LVM), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF) were determined by two-dimensional echocardiography. The mean follow-up was 513 ± 159 days. Changes in continuous parameters were tested by the t test, changes in discrete characteristics are presented by means of transition tables and tested with the McNemar test. RESULTS: The mean LVEF was 59.3 ± 9.9 %, both mean LVM (238.6 ± 101.5 g) and LVMI (54.0 ± 23.6 g/m(2.7)) were increased while relative wall thickness (RWT, 0.46 ± 0.18) indicated the presence of concentric LVH. Of the patients, 10.2 % displayed renal dysfunction (estimated GFR < 60 ml/min/1.73 m(2)). The 1.5-year overall mortality was 1.2 %. Compared with discharge, at follow-up the proportion of patients with blood pressure (BP) values < 140/90 mmHg decreased from 68.7 % to 55.0 % (p < 0.001) and with low-density lipoprotein (LDL) values < 100 mg/dl from 62.6 % to 38.1 % (p < 0.001). At follow-up significantly more patients displayed a GFR value of < 60 ml/min/1.73 m(2) (10.2 % vs. 16.0 %, p < 0.001). CONCLUSION: A significant proportion of hypertensive rehabilitation participants displayed TOD including LVH and renal dysfunction. Even after stringent BP reduction, a considerable increase in nephropathy could be found after 18 months.

Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease.

Stroke is a complex disorder with a poorly understood multifactorial and polygenic aetiology. We used the stroke-prone spontaneously hypertensive rat (SHRSP) as a model organism, mated it with the stroke-resistant spontaneously hypertensive rat (SHR) and performed a genome-wide screen in the resultant F2 cohort where latency until stroke, but not hypertension (a major confounder) segregated. We identified three major quantitative trait loci, STR1-3, with lod scores of 7.4, 4.7 and 3.0, respectively, that account for 28% of the overall phenotypic variance. STR2 colocalizes with the genes encoding atrial and brain natriuretic factor, peptides with important vasoactive properties. Our results demonstrate the existence of primary, blood pressure-independent genetic factors predisposing to a complex form of stroke.

[Quality and appropriateness of pain medication. Instrument for estimation in nursing home residents]. / Qualität und Angemessenheit der Schmerzmedikation. Instrument zur Einschätzung bei Pflegeheimbewohnern.

BACKGROUND: The pain medication appropriateness scale (PMASD) was developed in 2006 in the USA to evaluate the quality and appropriateness of pain treatment in nursing home residents (NHR). This tool can be used to identify potential problems with the pharmacological treatment of pain. METHODS: We developed a German version (PMASD) adapted to the German setting and applied it in Germany to NHR with and without cognitive impairment for the first time. In agreement with the original instrument a test result of >67 % was considered as appropriate pain treatment. RESULTS: For the 560 analyzed NHR the average SPMAS score was 39±1,7 (range from -67 to +100). Overall 72% of the study population did not achieve the defined threshold for appropriate pain management. CONCLUSIONS: An appropriate tool for quantitative evaluation of pain treatment was so far not available in Germany. The PMASD analysis showed deficits of pain management in NHR. This tool showed good practicability in Germany and could provide a valuable tool for pain treatment in clinical research and practice.

Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors.

The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7-10 animals per group). After 6 weeks, D and D-FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D-FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D-FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFß) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis.

Antipsychotic drugs predominate in pharmacotherapy of nursing home residents with dementia.

INTRODUCTION: The aim of this study was to investigate the frequency of benzodiazepines, antidementia and antipsychotic drug prescriptions in nursing home residents (NHR).Data of a German health insurance company were retrospectively analyzed for the year 2008. METHODS: The study cohort comprised 13,042 NHR (82% women, mean age 83.6 ± 7 years). Following analgetics, antipsychotic drugs were the second most frequently prescribed drug group with 13.3% of all prescriptions. Dementia was diagnosed in 8 017 (61.5%) NHR. Thereof 51.6% received an antipsychotic, 17.3% a benzodiazepine and 15.2% an antidementia pharmaceutical, respectively. 18.1% of NHR with dementia and antipsychotic drug prescriptions were in combined treatment with antidementia pharmaceuticals. The rate of antipsychotic drug prescribing was significantly doubled in NHR with dementia compared to those without this diagnosis (p<0.01); the most frequently prescribed antipsychotics were melperone, risperidone and pipamperone. DISCUSSION: This study demonstrates the wide-spread use of psychotropic drugs in NHR. Moreover, dementia in NHR was associated with antipsychotic drug prescribing in every second patient. This highlights the need for further studies analyzing alternative treatments for dementia-related symptoms.

[Interdisciplinary guidance for pain management in nursing home residents]. / Interdisziplinäre Handlungsempfehlung zum Management von Schmerzen bei älteren Menschen in Pflegeheimen.

Pain management in nursing home residents (NHR) is insufficient. Hence, this guidance summarizes latest research results and guidelines of particular requirements on treatment of pain in the elderly. The purpose is to improve health care processes and outcomes on individual and institutional level. To reach this aim a multidisciplinary collaboration is essential. The prerequisite for adequate pain treatment is to conduct a standardized pain assessment. Likewise, the application of all opportunities of non-medical pain treatment strategies contributes to the reduction of occurrence of pain and therefore to the preservation of quality of life in NHR. Age-related changes in physiology may affect tolerance and effects of analgesics. Besides, drug interactions need to be considered. After all, education of NHR and involvement of their relatives in pain management foster successful management and treatment of pain.

[Pain, fear of falling and functional performance in nursing home residents - a cross-sectional study]. / Schmerzen, Sturzangst und funktionelle Fähigkeiten von Menschen in Pflegeheimen - eine Querschnittsstudie.

Pain and fear of falling (FOF) are modifiable factors that might play an important role in functional performance of nursing homes residents (NHR). Both factors are characterised by deficits in research and provision of long-term care services. The purpose of this study was to examine the functional performance of NHR with and without pain or FOF. Quantitative data were collected on NHR in Berlin and Brandenburg using a cross-sectional design. The cognitive status was assessed using the Minimental state test. Existing pain and FOF were assessed as a question part of interview. Functional performance was examined using the Barthel Index (BI) the Timed «up & go¼-Test. Multiple linear regression analyses were performed to investigate the research question and the influence of additional explanatory variables (age, sex, relevant somatic morbidity). 217 NHR without considerable cognitive impairment (MMST >= 20) participated. 65 % of the NHR suffered from pain and 48 % had FOF. There was a statistically significant association between Pain or FOF und lower functional mobility. With respect to NHR able to walk, there was statistically significant association between Pain or FOF und lower performance in activities of daily living. Possibilities for interventions which might have positive effects on functional performance of NHR are an improved pain treatment and interventions to reduce FOF.

[Use of health insurance data to analyse pain management practices in the nursing-home setting]. / Sekundärdatenanalyse von Routinedaten einer Krankenkasse - Ein Zugangsweg zur Beschreibung schmerzbezogener Versorgungsleistungen von Pflegeheimbewohnern.

Pain is the most common health-related complaint in older persons. International estimations mention up to 80% of nursing home residents suffering from pain. In the meantime, no reliable epidemiological data on pain in nursing home residents are available for Germany, because of restricted access to the nursing-home population. This pilot study aimed to evaluate whether routine data from a German statutory health insurance fund can be used to generate data on pain prevalence and analgesic therapy in nursing home residents. To this end, data of all insured persons of Deutsche BKK who received long-term care insurance benefits for nursing-home care between April and June 2007 were selected anonymously. These data were combined with data on diagnoses and analgesic prescriptions. 3 pain-related diagnoses were selected: R 52 (pain, not elsewhere classified), M 16 (coxarthrosis) and G 53.0 (postherpetic neuralgia) and analysed for corresponding prescriptions. The study sample shows similar characteristics regarding age distribution and care needs in terms of long-term care insurance benefits compared to the official data on nursing-home residents for Germany in 2007. The rate of dementia was within the expected range, too. Therefore, external validity of the sample is assumed. One of the 3 selected diagnoses had been documented in 15% of the sample. About 58% of those received an analgesic prescription. Deficits were discovered regarding the documentation of postherpetic neuralgia, the combination of different analgesics and prescriptions for adjuvant drugs. Prevalence rate and numbers of prescriptions were as frequent as expected. The routine method for this analysis proved to be practicable and reliable. Data quality is deemed sufficient so that the main study will proceed to include a longer period of time and additional data.

[Special features of pharmacotherapy in older hypertensive subjects]. / Besonderheiten der Pharmakotherapie beim älteren Hypertoniker.

The prevalence of arterial hypertension in Germany is 60-80% in individuals between 65 and 74 years of age. In older people there is also a positive correlation between blood pressure level and rise in mortality due to myocardial infarction and stroke. Antihypertensive therapy can considerably improve the prognosis of older hypertensive individuals. Treatment is of enormous importance in these patients, particularly for prevention of strokes, which will continue to increase in the future as a result of demographic trends. Older patients have an elevated risk of developing undesirable drug reactions while under therapy such as a drop in blood pressure in an erect/standing position. Taking into account individual risk factors for unwanted events and avoidance of drug interactions during polypharmacotherapy are important aspects in differential therapy with antihypertensive agents in the elderly.

CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine.

The CYP3A5*1 allele has been linked to high expression of CYP3A5 and metabolism of cyclosporine. We evaluated the role of CYP3A5*1 for long-term survival in renal transplant patients in a cohort of 399 patients who underwent cadaveric or living donor kidney allograft transplantation. All patients were treated with a similar cyclosporine-based immunosuppressive maintenance therapy protocol. The mean duration of follow-up was 8.6+/-3.7 years. In univariate survival analysis, the presence of the CYP3A5*1 allele in recipients significantly increased patient survival P=0.028 (log-rank), resulting in a hazard ratio (HR) of 0.52 (95% CI=0.29-0.94). When the presence of the CYP3A5*1 allele was included in multivariate Cox regression analyses accounting for major risk factors for patient death, CYP3A5*1 still conferred a protective effect. Further, haplotype analysis at the CYP3A5 locus confirmed that CYP3A5*1 might indeed be responsible for this survival benefit.